Detachable tip microcatheter

ABSTRACT

A microcatheter for delivering embolic agent to a vascular site is provided. The microcatheter has a biocompatible or biocompatible and biodegradable tip which can be detachably engaged to the microcatheter body by a thermoplastic sleeve. Once the embolic agent is delivered to the desired vascular site, the tip of the microcatheter is often entrapped within the mass of the liquid embolic fluid. Using the microcatheter, the clinician can retract the microcatheter at a predetermined retraction force thereby disengaging the tip from the microcatheter body allowing for easier removal of the microcatheter.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.12/543,857, filed Aug. 19, 2009 which claims priority to and the benefitof U.S. Provisional Patent Application No. 61/090,185, filed Aug. 19,2008, and U.S. Provisional Patent Application No. 61/090,188, filed Aug.19, 2008, the entire contents of each of which are incorporated hereinby reference.

FIELD OF THE INVENTIONS

This application relates to detachable tip catheters, including adetachable, biocompatible tip microcatheter having a thermoplasticsleeve.

BACKGROUND

Microcatheters, including neuromicrocatheters, are generally microtubesinserted into the body through a blood vessel such as the femoral arteryand have a variety of uses (see, e.g., U.S. Pat. Nos. 6,306,124 and6,454,738). Microcatheters have a distal and a proximal end where,typically, at or near the very distal end, a marker band is employed topermit the clinician to visualize the microcatheter positioning duringin vivo use. The marker band typically comprises a metal or metal alloyring such as platinum, nitinol and/or gold rings which can be visualizedvia fluoroscopy.

Microcatheters are typically used to embolize the neurovasculature suchas in treating arteriovenous malformations (AVMs), aneurysms, and thelike in a relatively non-invasive manner. See, for example, Jones, etal., (U.S. Pat. No. 5,843,050), which discloses a microcatheter fornegotiating small tortuous vessels or the neurovasculature.

A variety of microcatheters, suitable for the wide variety ofapplications, are available commercially. Neurovascular embolizationdevices include intravascular compositions which solidify in vivo so asto permanently occlude blood flow to cerebral aneurysms and cerebralarteriovenous malformations. Suitable intravascular compositionsinclude, by way of example only, cyanoacrylates which polymerize in vivoto form a solid mass as well as solutions of a biocompatible, waterinsoluble polymer dissolved in a non-aqueous solvent such as dimethylsulfoxide (“DMSO”) whereupon introduction into the vasculature, the DMSOdissipates and the polymer precipitates in the aqueous based bloodcomposition. Such intravascular compositions further comprise a contrastagent to assist in visualization of the formed mass.

One problem associated with microcatheter use particularly in effectingneurovascular embolization is the phenomena referred to as “reflux.”Typically, during neurovascular embolization, a solid mass is formedfrom an embolic agent, such as for example an embolic liquid, deliveredin situ to the embolization site. The embolic agent, in the form of aprepolymer such as a cyanoacrylate prepolymer or a polymeric solutionsuch as an Onyx® formulation (available from ev3 Neurovascular, Irvine,Calif. and comprises ethylene vinyl alcohol copolymer, DMSO andtantalum) is ejected distally from the microcatheter tip and forms asolid mass at this distal point. However, in certain cases, “flow back”or “reflux” of the liquid composition prior to solidification can occurand the embolic agent can engulf the microcatheter tip. In such cases,the microcatheter tip can be entrapped in the solid mass uponsolidification of the embolic agent. Even in instances where reflux isavoided, the microcatheter may become trapped in the blood vessel as aresult of vasospasm causes by the presence of DMSO or other spasmodicmaterials in the embolic composition.

When reflux or vasospasm occurs, the clinician is often reluctant to useexcessive force to remove the neuromicrocatheter for concerns overvessel tear or rupture. Typically, the clinician either must attempt towithdraw the neuromicrocatheter by force, often resulting inmicrocatheter breakage, or must cut the microcatheter. In either event,a portion of the neuromicrocatheter remains in the patient'svasculature. Alternatively, the clinician can attempt to minimize refluxby underfilling the cavity thereby leaving less than a desirabletherapeutic outcome and yet not completely eliminating the risk of atrapped neuromicrocatheter.

SUMMARY

An aspect of at least one of the embodiments described herein includesthe realization that it is advantageous to provide microcatheters whichcan be safely removed from the patient in the event that they becometrapped in the vasculature for any reason, while minimizing thepotential deleterious effects caused by such complications. It isfurther advantageous to provide microcatheters which can maintain a highburst strength so as to inhibit the microcatheters from separating orbursting during the injection of the embolic agent, as well as a lowretraction force for removal of the microcatheter in the event of refluxeither before and/or after delivery of the embolic agent.

Thus, in accordance with at least one embodiment, a method for usingmicrocatheter can comprise advancing a microcatheter into the patient,the microcatheter comprising an elongate flexible tubular body having aproximal end, a distal end and at least one lumen extending axiallythere through, a tip body having a proximal end and a distal end and alumen extending axially there through, and a thermoplastically fittedsleeve covering a distal end of the tubular body and a proximal end ofthe tip body. The method can further comprise placing the tip body atthe vascular site, delivering the embolic agent through the lumen of thetubular body and the lumen of the tip body, and detaching the tip bodyfrom the tubular body by applying a retraction force to the tubularbody, the tip body remaining with the embolic agent.

In accordance with another embodiment, a microcatheter for deliveringembolic agent to a vascular site within a patient can comprise anelongate flexible tubular body having a proximal end, a distal end andat least one lumen extending axially there through, a tip body having aproximal end and a distal end and a lumen extending axially therethrough, and a thermoplastically fitted sleeve covering a portion ofboth the tubular body and tip body, wherein the sleeve is frictionallyengaged with both the tubular body and tip body, and the tip isdetachable from one of the tubular body and tip body by application of aretraction force.

DETAILED DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present embodiments willbecome more apparent upon reading the following detailed description andwith reference to the accompanying drawings of the embodiments, inwhich:

FIG. 1A is a side elevation view of a microcatheter according to oneembodiment.

FIG. 1B is an enlarged view of a tip detachment portion of themicrocatheter of FIG. 1A.

FIG. 2A is a schematic view of a positioning method using themicrocatheter of FIG. 1A to treat an aneurysm.

FIG. 2B is an enlarged view of a portion of the microcatheter of FIG. 1Ashowing the microcatheter tip body and thermoplastic sleeve detachablyreleased from the microcatheter tubular body.

FIG. 2C is an enlarged view of a portion of the microcatheter of FIG. 1Ashowing the microcatheter tip body detachably released from themicrocatheter tubular body and thermoplastic sleeve.

FIG. 2D is a schematic view of an arteriovenous malformation.

FIG. 2E is a schematic view of a positioning method using themicrocatheter of FIG. 1A to treat the arteriovenous malformation.

FIG. 3 is a schematic view of the microcatheter tubular body, the tipbody, and the thermoplastic sleeve of FIG. 1A.

FIG. 4 is a schematic view of the thermoplastic sleeve of FIG. 1Adetachably engaged to the microcatheter tubular body.

FIG. 5 is a schematic view of the thermoplastic sleeve of FIG. 1Adetachably engaged to the microcatheter tubular body and the tip body.FIG. 5 also shows side holes in the tip body.

FIG. 6 is a schematic side view of a microcatheter according to anotherembodiment.

FIG. 7A is an enlarged cross-sectional view of a tip detachment area ofthe microcatheter of FIG. 6.

FIG. 7B is a perspective cross-sectional view of a sleeve according toanother embodiment.

FIG. 7C is a perspective cross-sectional view of a sleeve according toanother embodiment.

FIG. 8 is an enlarged cross-sectional view of the tip body of themicrocatheter of FIG. 6.

FIG. 9 is a chart illustrating the relationship between burst strengthand detachment force for the microcatheter of FIG. 6.

FIG. 10 is a cross-sectional view of a portion of a microcatheteraccording to another embodiment, including a thin-walled detachmentportion.

FIG. 11 is a cross-sectional view of a portion of a microcatheteraccording to another embodiment, including a detachment ring.

FIG. 12 is a cross-sectional view of a portion of a microcatheteraccording to another embodiment with a separately manufactureddetachable tip.

FIG. 13 is a cross-sectional view of a portion of a microcatheteraccording to another embodiment, showing a tip having side holes.

FIG. 14 is a perspective view of a portion of a microcatheter accordingto another embodiment, showing a catheter tip comprising grippingstructures.

FIG. 15 illustrates is a schematic side view of a microcatheteraccording to another embodiment having a detachable tip, side holes, andmarker bands.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art. Although any methods and materials similar or equivalent tothose described herein can be used in the practice or testing of theembodiments described herein, the preferred methods, devices, andmaterials are now described. All publications and patent applicationscited herein are incorporated herein by reference in their entirety.

It must be noted that as used herein and in the appended claims, thesingular forms “a,” “an,” and “the” include plural references unless thecontext clearly dictates otherwise.

Detachable Tip Microcatheter with Thermoplastic Sleeve

With reference to FIG. 1, a microcatheter 10 (e.g. a neuromicrocatheter)can be useful for delivering embolic agents to vascular sites ofpatients. Typically, these vascular sites are located in theneurovasculature, and include AVMs and aneurysms. However, thistechnique can be used in any vessel in the body, and can be useful forembolizing any body lumen. Microcatheter 10 can comprise a distal end12, a proximal end 14, and an elongate flexible tubular body 16extending therebetween.

The distal end 12 of the microcatheter can be comprised of abiocompatible tip body 30 which is detachably engaged and coaxial withthe tubular body 16 by a sleeve 26, such as for example a thermoplasticsleeve (see, e.g. FIG. 1B). What is meant by “detachably engaged” isthat the tip body 30 is engaged with or attached to the tubular body 16;however, the two may be disengaged or detached upon application of aretraction force that may be predetermined. What is meant by “retractionforce” is generally a tensile force applied along the longitudinal axisof the microcatheter 10 (e.g., parallel to the central lumen 22) in theproximal direction (e.g., in the direction that would withdraw themicrocatheter from the patient). The retraction force used to detach thetubular body 16 from the tip body 30 can, for example, be no more thanabout 160 gram-force and more preferably can range from about 10 toabout 160 gram-force. In certain embodiments, the retraction force isabout 20 gram-force to about 40 gram-force. In other embodiments, theretraction force is about 30 gram-force to about 50 gram-force. Otherranges than those described above can also be used. The tubular body 16and the tip body 30 can be of the same or different outer and innerdiameters. The proximal end 14 of microcatheter 10 can be provided witha manifold 18. Manifold 18 can be provided with at least one access port20 in fluid communication with a distal access port 24 by way of anelongate central lumen 22. Central lumen 22 allows for the microcatheter10 to track over a guidewire (not shown). After removal of theguidewire, the central lumen 22 may be used to deliver an embolic agentto the desired vascular site.

To further assist in the delivery of the embolic agent to the desiredvascular site, the tip body 30 may optionally contain a plurality oflateral apertures or holes 38. The shape of the apertures 38 can beselected from round, elliptical, or other shapes.

Also shown in FIG. 1B is the central lumen 22. Although not specificallyillustrated, the microcatheter may contain a plurality of lumens. Forexample, one lumen may be dedicated for use by a guidewire, whileanother lumen may be dedicated to delivery of the embolic agent. Themicrocatheter 10 can contain a marker 32, for example a radiopaquemarker, located on the distal end 34 of the tubular body 16. The marker32 can be a ring or band made from a metal or metal alloy, such asplatinum, platinum/iridium, gold, nitinol and the like.

FIG. 2A shows the use of the microcatheter 10 within the human body.Specifically, the microcatheter 10 is inserted into the patient in aconvenient location, such as the groin. Various positioning systems canbe used, such as a guide microcatheter, and a guidewire may also beemployed to assist with the positioning. The microcatheter 10, oranother microcatheter described herein, can be moved through thevascular until the tip body 30 reaches a treatment site 40, such as forexample an AVM or aneurysm. The position of the microcatheter 10 can bemonitored by visualizing the radiopaque marker 32. Once themicrocatheter 10 is in its appropriate position in the vasculature,embolic agent 42 can be delivered to the treatment site 40. The embolicagent 42 can be a liquid embolic agent and can comprise of a number ofmaterials. Suitable embolic agents 42 include those containingbiocompatible polymers and prepolymers which polymerize in situ. Theliquid embolic agent can also comprise a biocompatible solvent and acontrast agent. In one embodiment, the contrast agent iswater-insoluble. One such example is Onyx®, a non-adhesive liquidembolic agent comprised of EVOH (ethylene vinyl alcohol) copolymerdissolved in DMSO (dimethyl sulfoxide) and suspended micronized tantalumpowder to provide contrast for visualization under fluoroscopy. Furtherdescription of suitable embolic agent are described in U.S. Pat. Nos.5,667,767; 5,695,480; 6,051,607; 6,342,202; 6,531,111; and 6,562,317 allof which are incorporated by reference herein and made a part of thisspecification.

Referring to FIG. 2A, after delivery of the embolic agent 42, the tipbody 30 can be entrapped within the agent 42. In certain embodiments,the sleeve 26 can also be entrapped or partially trapped by the agent42. To remove the microcatheter 10 from the patient, the attendingclinician can apply a retraction force to the tubular body 16. When theretraction force is applied, the thermoplastic sleeve 26 can either 1)remain attached to the tip body 30 (FIG. 2B); 2) remain attached to thetubular body 16 (FIG. 2C); or 3) break into two components therebyremaining partially attached to both the tubular body 16 and the tipbody 30 (not shown).

Similarly, the microcatheter 10, or another microcatheter describedherein, can be used to treat an arteriovenous malformation (AVM). FIG.2D illustrates an example of an AVM, and FIG. 2E illustrates how themicrocatheter 10 can be moved to the AVM site to deliver embolic agent42 to the site. Similar to FIGS. 2A-C, the tip 30 can be detachedthrough use of the sleeve 26 and a retraction force.

The location of the sleeve 26 after application of the force can beinfluenced by the construction of how the sleeve 26 is engaged to thetip body 30 and the tubular body 16 (see FIG. 3). The engagement of thetip body 30 to the sleeve 26 and the engagement of the tubular body 16to the sleeve 26 can be accomplished in variety of ways. For example,the sleeve 26 can overlap with a distal end 34 of the tubular body 16(see FIG. 4) and/or can overlap with a proximal end 36 of the tip body30 (see FIG. 5). The amount of overlap can be a factor in determiningthe retraction force used for detaching the tip body 30. In someembodiments, one or both attachments of the sleeve 26 to the tip body 30or the tubular body 16 can be a butt joint (end to end). In someembodiments, the distal end 34 and proximal end 36 can form a buttjoint.

One advantage of the microcatheters described herein is the ability tohave a low and consistent detachment force while maintaining a highburst strength. In addition to the use of the sleeve 26 to detachablyengage the tip body 30 to the tubular body 16, this advantage can alsobe accomplished by the materials selected for the tubular body 16 andthe sleeve 26, the overlap length of the sleeve 26 with the tubular body16 and the tip body 30, and/or the construction of affixing the sleeve26 to the tubular body 16 and the tip body 30.

The tubular body 16 can be constructed of a variety of materials and ina variety of ways known in the art to optimize the burst strength. Inone embodiment, the tubular body 16 can be constructed of a materialthat is compatible with dimethylsulfoxide. The tubular body 16 can alsocontain zones with varying flexibility which can also be controlled bythe methods of construction and materials employed. It can be desirableto have a more flexible zone at the distal end of the tubular body 34.Description of the construction of the zones can be found in U.S. Pat.No. 5,843,050, which is hereby incorporated by reference and made a partof this specification. The tubular body 16 can be constructed bylayering various polymers, such polyimide, polytetrafluoroethylene,polyether block amides, polyamide and the like. The tubular body 16 canalso optionally include a braid of varying pitches to enhance the burststrength. Description of the braid can be found, for example, in U.S.Publ. 2004-0153049, which is hereby incorporated by reference and made apart of this specification.

The tip body 30 can be made from a biocompatible material. What is meantby “biocompatible” is that the material, in the amounts employed, aresubstantially non-toxic and substantially non-immunogenic when usedinternally in the patient. A biocompatible material can includeshrink-tubing polymers, for example, polyethylene block amides,including those branded Pebax®.

In certain embodiments, the tip body 30 can also be “biodegradable.” Awide variety of biodegradable/bioerodable and non-biodegradablematerials are known which are useful for constructing microcathetertips. The tip body 30 can be formed of a material which is biodegradableor bioabsorbable in situ. Biodegradable or bioabsorbable materials, orsome combination thereof, can be used which allow for thebiodegradation/bioabsorption in predetermined conditions.

A variety of biocompatible-biodegradable materials are commerciallyavailable. The general criteria for selecting a polymer for use as abiomaterial is to match the mechanical properties and the time ofdegradation to the needs of the application. Polymeric substances whichmay be used are set forth in U.S. Pat. No. 4,938,763. For example, thefollowing polymers are biocompatible as well as biodegradable:

DLPLA—poly(dl-lactide)

LPLA—poly(l-lactide)

PGA—polyglycolide

PDO—poly(dioxanone)

PGA-TMC—poly(glycolide-co-trimethylene carbonate)

PGA-LPLA—poly(l-lactide-co-glycolide)

PGA-DLPLA—poly(dl-lactide-co-glycolide)

LPLA-DLPLA—poly(l-lactide-co-dl-lactide)

PDO-PGA-TMC—poly(glycolide-co-trimethylene carbonate-co-dioxanone)

One such class of absorbable material which may be suitable is thepolyhydroxyalkanoate class of biopolymers (“PHA”). For example one suchPHA is produced recombinantly, and branded TephaFLEX polymer, currentlyavailable from Tepha, Inc. Cambridge Mass., USA.

The sleeve 26 can be comprised of a thermoplastic material or a materialthat is heat-shrinkable. The thermoplastic selected is ideallycomplimentary to the tubular body 16 material and may be either filledor unfilled. The sleeve 26 can comprise more than one thermoplasticmaterial. Examples include thermoplastic polyolefin elastomer (TPE);acrylic; celluloid; cellulose acetate; ethylene-vinyl acetate (EVA);ethylene vinyl alcohol (EVAL); fluoroplastics (PTFE, FEP, PFA, CTFE,ECTFE, ETFE); ionomers; acrylic/PVC alloy; liquid crystal polymer (LCP);polyacetal (POM or Acetal); polyacrylonitrile (PAN or acrylonitrile);polyamide (PA or Nylon); polyaryletherketone (PAEK or Ketone);polybutadiene (PBD); polybutylene (PB); polycaprolactone (PCL);polychlorotrifluoroethylene (PCTFE); polyhydroxyalkanoates (PHAs);polyketone (PK); polyester; low density polyethylene (LDPE); linear lowdensity polyethylene (LLDPE); polyethylene (PE); polyetherimide (PEI);polyethersulfone (PES); polysulfone; polyethylenechlorinates (PEC);polylactic acid (PLA); polymethylpentene (PMP); polyphenylene oxide(PPO); polyphenylene sulfide (PPS); polyphthalamide (PPA); polypropylene(PP); polystyrene (PS); polyvinyl chloride (PVC); polyvinylidenechloride (PVDC); and combinations thereof.

The sleeve 26 can be filled or not filled with a radiopaque material,such as barium sulfate.

In one embodiment, the thermoplastic is a thermoplastic elastomer. Inone embodiment, the thermoplastic is a heat shrinkable polyolefin, suchas polyethylene and in another embodiment the thermoplastic is a lowdensity polyethylene and polyolefin elastomer (DuPont Engage®) blend.

As mentioned above, the ability to detach the tip body 30 from thetubular body 16 can be influenced by the construction of themicrocatheter 10 and particularly, the construction of detachablyengaging the sleeve 26 to the tip body 30 and the tubular body 16. Thetotal length of the microcatheter 10 can generally be in the range ofform about 150 cm to about 175 cm, although other ranges are alsopossible. The tubular body 16 can be selected to have an outsidediameter within the range of from 0.5 mm to about 1.5 mm, although otherdiameters are also possible. In some embodiments, the diameter of thecentral lumen 22 can be about 0.002 to about 0.005 inches larger thanthe outside diameter of the guidewire, if one is used. This diameter canbe modified appropriately at the proximal and distal ends. Otherdimensions than those described herein can be readily utilized by thoseof ordinary skill in the art in view of the disclosure herein to suitparticular intended uses of the microcatheter 10.

The tubular body 16 and tip body 30 can be provided as described above.The sleeve 26 can then be provided and detachably engaged to the tubularbody 16 and the tip body 30 by applying a controlled temperature heatsource for a designated time at the juncture of the sleeve 26 and thetubular body 16 and the tip body 30. The time that the heat source isapplied, as well as the temperature, can influence the bond that formsbetween the sleeve 26 and the other components. When the heat source isapplied, the sleeve 26 can attach to the tubular body 16 and the tipbody 26 by either a mechanical bond (force of the heat shrinking aroundthe smaller microcatheter and tip body) or a fused bond (where thematerials of the sleeve, the tubular body, and/or the tip body aremelting together). The bond can be a weaker tensile strength bond toallow the tip body 30 to detach from the tubular body 16 uponapplication of a retraction force of about 10 to about 160 gram-force,preferably about 20 to 50 gram-force.

In an alternative method of construction, the sleeve 26 can be attachedto the tip body 30 and/or tubular body 16 by use of adhesives orsolvents.

As described above, there can be varying amounts of overlap of thesleeve 26 with the tubular body 16 and/or the tip body 30. The amount ofoverlap can be one factor in the retraction force required to separatethe tip body 30 from the tubular body 16. The larger the overlap of thesleeve 26 on either the tubular body 16 and/or the tip body 30, thegreater the retraction force required to detach the two components. Insome embodiments, this overlap can be from about 0.5 to about 5 mm. Insome embodiments, the overlap can be about 2 to about 4 mm. Otheroverlap ranges are also possible.

A kit comprising a microcatheter 10, or other microcatheter describedherein, and a liquid embolic agent as described above can be provided.

With reference to FIGS. 6-8, a microcatheter 110 can be similar to themicrocatheter 10 described above. Therefore, similar components of themicrocatheter 110 are referenced by the same reference numeral as thecorresponding component in the microcatheter 10, incremented by onehundred.

With reference to FIG. 7A, a tip detachment area can comprise a tubularbody 116, a thermoplastically fitted sleeve 126, and a tip body 130. Thethermoplastic sleeve 126 can be fitted over a distal end 134 of thetubular body 116 and proximal end 136 of the tip body 130, similar tosleeve 26 described above. In some embodiments, the sleeve 126, or anysleeve described herein, can be frictionally engaged with both thetubular body 116 and tip body 130 prior to detachment, and can form atighter frictional engagement with the tubular body 116 than with thetip body 116. Once a retraction force is applied, the sleeve 126 canthus tend to remain on the tubular body 116, thus leaving the tip body130 behind.

With continued reference to FIG. 7A, the tubular body 116 can comprise amarker 132. The marker 132 can be positioned such that it liesunderneath the sleeve 126, thereby identifying a position of the sleeve126 and tip body 130 prior to detachment of the tip body 130.

FIG. 7B illustrates an alternative embodiment of a sleeve 126′. Thesleeve 126′ can be similar to the sleeve 126 described above, except thesleeve 126′ can include an internal separation element 127. The internalseparation element 127 can be designed to separate the distal end 134and proximal end 136 of the tubular body 116 and tip body 130,respectively, while still allowing embolic agent to flow through themicrocatheter. The separation described above can inhibit the distal end134 and proximal end 136 from contacting one another and/or sticking oradhering to one another after heating of the thermoplastically fittedsleeve 126′. If the distal end 134 and proximal end 136 stick to oneanother, the amount of detachment force required to separate them canincrease. Thus, the separation element 127 can facilitate reduceddetachment forces. The separation element 127 can be formed integrallywith the sleeve 126′, or can be attached or inserted separately. Theseparation element 127 can comprise a variety of materials, includingbut not limited to metal or plastic, and in some embodiments can be inthe shape of a washer.

FIG. 7C illustrates another alternative embodiment of a sleeve 126″. Thesleeve 126″ can be similar to the sleeves 126′ and 126″ described above,except that the sleeve 126″ can comprise two discrete components 128 aand 128 h. The components 128 a and 128 b can be mirror images of oneanother, and can be attached (e.g. adhered together or held together) toform the sleeve 126″. As with the sleeve 126′, the sleeve 126″ caninclude separation elements 127 which can be used to separate the distalend 134 and proximal end 136 of the tubular body 116 and tip body 130.

With reference to FIG. 8, the tip body 130 can also comprise a marker133. The marker 133 can be a radiopaque marker located along a portionof the tip body 130, and can be used to identify a position of the tipbody 130 prior to and/or after detachment of the tip body 130 from thetubular body 116.

With reference to FIG. 9, a chart illustrating the relationship betweenstatic burst strength and detachment force for the microcatheter ofFIGS. 6-8 is provided. Static burst strength, as described above,generally describes an internal pressure (for example applied by embolicliquid within the catheter) which can cause radial bursting of themicrocatheter. Static burst strength is that pressure at which themicrocatheter's tubular wall bursts. It is generally desired to have ahigh static burst strength, so as to limit the possibility of themicrocatheter bursting during use. If the static pressure is raised highenough, this internal pressure can cause the microcatheter to burst, orbreak. Static burst strength can be tested, for example, by clamping orotherwise securing both ends of a microcatheter tube, injecting liquidinto the microcatheter, and allowing the static pressure inside themicrocatheter to press radially against the tubular wall. Static burststrength can also be tested at various stages, for example, prior to afirst use of the device and/or after use of the device for a givenperiod of time (e.g. after pushing embolic agent through themicrocatheter 110 during a simulated one hour procedure). Generally,prior to first use a higher burst strength can be achieved for a givendetachment force. FIG. 9 represents a static burst test conducted afterapproximately one hour of simulated use of the microcatheter 110.

Detachment force, as described above, generally describes an axiallyapplied tensile force required for detaching the tip body 130 from thetubular body 116. Detachment force can be applied by the user, forexample by pulling proximally on a proximal end of the tubular body 116.It is generally desired to have a low detachment force, so as to limitthe amount of force required to detach the tip body 130.

One potential problem when dealing with burst and detachment at the sametime is the possibility of bursting at the intersection between thetubular body 116 and the tip body 130. Thus, a mechanism such as one ofthe sleeves described above can act to both inhibit bursting of themicrocatheter 110, while facilitating detachment of the tip body 130.For example, the sleeve 26, 126, 126′, or 126″ can allow for a desireddetachment force while maintaining a high burst strength.

As the chart in FIG. 9 illustrates, in one embodiment the detachmentforce for maintaining a static burst strength between approximately 50and 400 psi can range from approximately 20 to 40 gram-force while usingthe sleeve 126′. Thus, if the sleeve 126′ is thermoplastically fittedaround the tubular body 116 to such a degree that the retraction forcerequired for detachment increases (i.e. a tighter fit), so too will theamount of static pressure required to burst the microcatheter radially.In certain embodiments, the microcatheter 10 or 110 can be designed tohave a sufficiently high burst strength, for example in the range ofabout 150 psi to 450 psi, and more preferably at least 250 psi, with anassociated desired detachment force for example between about 24 and 54gram-force, and in certain embodiments no more than about 40, 35, 30 or25 gram-force. In certain embodiments, the microcatheter 10 or 110 canexhibit a burst strength of between about 150 psi to 225 psi withdetachment forces less than about 30 gram-force. In certain embodiments,the microcatheter 10 or 110 can exhibit a burst strength of about 275psi at a detachment force between about 32 to 33 gram-force.

The microcatheters 10 and 110 described above include thermoplasticallyfitted sleeves 26, 126, 126′ and 126″ which are used for detachablyengaging the tubular bodies and tip bodies of the microcatheters.Thermoplastically fitted sleeves can provide an advantage over othertypes of structures or systems for detachably holding a tip body to atubular body of a microcatheter. For example, metallic sleeves (e.g.metallic rings) can be used which require an adhesive to bond the ringto the distal end of the tubular body and tip body. However, theadhesive used with such metallic rings could undesirably deteriorate,allowing the metallic ring to dislodge from the microcatheter and becomean emboli in the patient's body. Additionally, using adhesive in thismanner requires that the adhesive be broken down before detachment. Ifthe adhesive is broken down by the embolic agent itself, the procedureof detachment can become time-dependent and take longer than desired, orin some cases could be unpredictable in terms of the time required fordetachment. Additionally, the retraction force needed to detach the tipbody could vary, depending on the amounts of adhesive used, theconsistency of the adhesive used, the application of the adhesive, etc.In contrast, the microcatheters described above have the advantage ofutilizing a single retraction force to quickly, efficiently, andconsistently detach the tip body from the tubular body of themicrocatheter.

Furthermore, in some embodiments the sleeves 26, 126, 126′, and 126″described above can have length (e.g. axially along the inner lumen) toouter diameter ratios which provide a further advantage in inhibitingbursting of the microcatheters 10 or 110. For example, in certainembodiments, the sleeve 126′ can have a length to outer diameter ratioof approximately 8:1 at a distal end, and 9:1 at a proximal end. Otherratios are also possible. In certain embodiments, the length to outerdiameter ratio is at least 6:1 or 7:1. Ratios for example as large as8:1 or 9:1 can provide added stability to the microcatheter, and inhibitbursting by providing greater coverage or overlap along the tubular body116 and tip body 130.

Additionally, having a length to outer diameter ratio which is larger onthe proximal end as compared to the distal end of the sleeve 126′ canfacilitate a tighter fit of the sleeve 126′ about the tubular body 116as compared to the tip body 130. This difference in fit can facilitatedetachment of the tip body 130, while allowing the sleeve 126′ to remainattached to the tubular body 116 after detachment.

With reference to FIG. 10-15, other types of detachable tip catheterscan be used to deliver an embolic agent. The components of the cathetersillustrated in FIGS. 10-15 and described herein can, at least in someembodiments, be used with the catheters 10 and 110 described above.

As described above, catheters are generally constructed according toknown principles of catheter design and typically consist of aproximally-disposed rigid section, an intermediate semi-flexiblesection, and a distal flexible portion designed to facilitatenegotiation of the small, tortuous vessels expected to be encounteredduring each particular medical application. The distal end of a cathetercan contain one or more radiopaque markers to aid a clinician invisualization of the catheter location during a medical procedure.Typically, the radiopaque markers are positioned at fixed distances fromthe distal end of the catheter. For example, one radiopaque marker canbe optionally placed proximally adjacent to a tip detachment area inorder to aid the clinician in visualizing the catheter and anatomicalsequela of the medical procedure (e.g., embolization) and tipdetachment.

Some catheters comprise a unibody catheter with a detachable tip. Theterm “unibody”, as used herein, is a broad term referring generally to acatheter or component that is manufactured as a single element. It isrecognized that a “unibody catheter” does not imply that the entirecatheter device consists of a single element. Rather, a “unibodycatheter” refers to the unibody construction of a portion of the distalend of the catheter, including a predetermined detachment area anddetachable tip region.

The predetermined tip detachment area may be, in essence, a weak orrigid portion of the catheter body. Put another way, the predeterminedtip detachment area may be less resilient with applied force than thetubular body. This unibody construction can be similar to traditionalcatheter tip design except that the weak/rigid construction of thepredetermined detachment point controls the location of breakage. Thisdesign improves upon existing unibody catheter tip construction in whichthe tip is substantially uniform and breakage occurs randomly along thecatheter tip body, upon the application of excessive force. In practice,the catheter can deform while inserted into the patient, particularly ina microvasculature environment. The catheter can be relativelyinflexible or flexible at the predetermined tip detachment area. Thusthe catheter tip can selectively detach at this predetermined area dueto the detachment area having a lower tensile strength than the adjacenttubing.

Resilience properties of the predetermined detachment area, such aselasticity (reversible deformation) or plasticity (non-reversibledeformation) can be calculated to occur per unit force at apredetermined tubular body location largely based on the physicochemicalproperties of the materials and the conditions under which the catheteris used.

In one configuration, the predetermined detachment area can be made ofthe same material as the catheter, but the detachment area is thinnerthan the adjacent portions of the catheter, providing a weakened pointsusceptible to breakage upon the application of an appropriate (e.g.,retraction) force. The relative weakness of the detachment area, and theconcomitant difference in thickness of the catheter wall can be modifiedin order to facilitate detachment (i.e., breakage) upon application ofthe desired amount of force. Typically, the detachment area will be atleast 10%, 20%, 30%, 40%, 50%, 65%, or 80% thinner than the adjacentcatheter wall.

Alternatively, the predetermined detachment area can be constructed of adifferent material than the proximally adjacent catheter body. Asdescribed above, the detachment area can be weaker and/or more rigidthan the catheter body immediately proximal to it in order that thecatheter preferentially breaks at the detachment area. The catheter tipbody (i.e., distal to the detachment area) can be the same material asthe catheter body, the same material as the detachment area, or adifferent material.

FIG. 10 is a schematic illustration of a unibody catheter 210 having adetachable tip constructed according to the principles described above.The catheter 210 forms a tubular body consisting of substantiallyparallel walls 214 forming a lumen 212. The material of the catheterwalls 214 are weakened at the detachment area 218. This weakening of thedetachment area 218 can be a thinning of the catheter wall 214 material,a different (weaker or more rigid) material compared to the catheterwall 214 material. The detachable tip 216 can be the portion of thecatheter 210 that is distal to the detachment area 218 and is detachedwith the breakage of the catheter 210 at the detachment area 218 uponapplication of predetermined force to the catheter 210. A marker 215 canbe positioned just proximal to the detachment area 218 and preferably ispositioned within 1 centimeter of the detachment area 218.

FIG. 11 shows an alternative embodiment of a unibody catheter 220 havinga predetermined detachment area. In this alternative embodiment, adetachment ring 228 is embedded in the catheter wall 214 at thepredetermined detachment area 218. The detachment ring 228 can serve aspoint of weakness which effects detachment of the tip 216.Alternatively, the detachment ring 228 can be attached to a guidewire(not shown), under control of the operator which, when effected, causescatheter 220 breakage at the detachment area 218. Typically, thedetachment ring 228 can be designed to remain with the distal catheterwall 214, but it can also be designed to detach and remain with the tip216. Again, marker 215 can be positioned just proximal to the detachmentarea 218 and preferably can be positioned within 1 centimeter of thedetachment area 218.

In some embodiments the tip 216 can be detached via electrolyticdetachment. A ring of electrically resistive material can be imbedded inthe catheter at the detachment area 218. When an electrical current ispassed through the ring, the resistive material can heat, melting thecatheter at the detachment area 218 and releasing the tip 216.

Some catheters can have detachable tips which are separatelymanufactured and affixed to the distal end of the catheter. Thedetachable tips can be constructed of the same or different material asthe catheter body. Biodegradable/bioerodable detachable tips, asdescribed herein, are preferred.

Optionally, the distal end of the catheter can be configured to receivea detachable tip. The design of the catheter and tip can facilitateseparation upon application of a predetermined amount of force.

FIG. 12 shows one embodiment of a catheter 230 with a separatedetachable tip 236. The distal catheter end is enlarged to form a flange238 and the detachable tip 236 is fitted over the flange as an integralconcentric coupling (i.e., in a sleeve-like fashion). Optionally, thedistal catheter end does not contain a flange or other specializedreceiving structure (i.e., has substantially the same outer diameter asthe adjacent portion of the distal catheter). The tip 236 can be weaklybonded or press or heat fitted (such as heat welded or shrink-wrapped)to the tubular body of the catheter, with a predetermined bond strengthallowing for a predetermined force for removal, similar to sleeves 26and 126 described above.

The tip 236 can be fitted with a “locking” design such that the tip 236is protected from inadvertent removal until a predetermined time. Wherethe catheter tip 236 reaches the desired location, the tip 236 can be“unlocked” from the underlying catheter body. A type of lock, such as anundercut, flange-lock, or luer-lock, or other means as available in thestate of the art can be used. The unlocking means can be mechanical, orit can be fully or partially electronic, such as remote means forinstituting the mechanical unlocking as described more fully herein.Thus, as a separate element, the tip 236 can have as a surface feature aprotrusion or intrusion capable of forming a lockable assembly with thecatheter tubular body.

In another embodiment, the catheter can contain a predetermineddetachment area as described herein and the separate tip can be attachedto the catheter distal to the detachment area. In this embodiment, theforce required to cause structural failure (breakage) at thepredetermined detachment area can be less than the force required todetach the tip from the catheter.

For most in vivo uses of the catheters described herein, includingcatheters 10 and 110, the tip (i.e. tip body) can be designed to bedetached upon the application of a force of about 10 to about 160gram-force, although the force can depend largely on the environment andcharacteristics of the catheter and tip. Typically, the detaching forcecan be applied by retraction of the catheter with a force sufficient toeffect tip detachment. The detachment force can be selected such thatthe tip will not detach under conditions of normal catheter use (i.e.,normal traction associated with positioning the catheter), but willdetach with a smaller amount of traction force than would be expected todamage the vessel in which the catheter is placed. This is aparticularly important consideration when the tip is trapped(accidentally or by design) in an embolic polymer or under conditions ofvasospasm.

Detachable tips can be designed to be purposely embedded in the embolicpolymers. In one design, as shown in FIG. 13, the tip can contain one ormore “side holes” 243 in order that embolic agent (e.g. embolic polymer)or other injected material flows laterally out of the catheter 240. Sucha tip can have only side holes 243, or can have both side holes 243 anda standard terminal opening 245 at a distal terminus of the catheter tip216. In practice, such a tip can be used to deliver an amount of theembolic polymer first from a side hole 243 which is first allowed toharden, followed by delivery of additional embolic polymer through theterminal opening 245. Desirably, the side hole 243 delivers polymer intoan AVM or aneurysmal sac and the terminally-delivered polymer continuesto fill an area distal the tip. Such a procedure is designed to entrapthe catheter tip in the embolic polymer, necessitating tip detachment.The force required for detachment should be less than would be expectedto cause damage to the vessel or dislodge the embolic polymer.

In general the detachable tip can have other features which aredecorative or functional. For example, FIG. 14 illustrates a detachabletip 256 with side grips 257. The side grips 257 can be used formechanical removal via a guidewire looped around the end of thedetachable tip 256. The side grips 257 can be protrusions orinvaginations designed to further anchor the tip 256 in an embolicpolymer when tip detachment is desired, as described herein. The sidegrips can also be used to aid in the mechanical retrieval of the tiponce it has been detached from the catheter. Alternatively, the designof the grips can add no function apart from decorative to give themedical device an aesthetically pleasing design.

A wide variety of biodegradable/bioerodable and non-biodegradablematerials are known which are useful for constructing catheter tips. Forseparately manufactured tips, shrink-tubing polymers can be usedincluding, for example, polyethylene block amides, including thosebranded Pebax®, polyamide, polyolefines, etc.

Alternatively, the tip can be formed of a material which isbiodegradable or bioabsorbable in situ. Biodegradable or bioabsorbablematerials, or some combination thereof, may be used which allow for thebiodegradation/bioabsorption in predetermined conditions.

A variety of biocompatible-biodegradable materials are commerciallyavailable. A general criteria for selecting a polymer for use as abiomaterial is to match the mechanical properties and the time ofdegradation to the needs of the application. Polymeric substances whichcan be used are set forth in U.S. Pat. No. 4,938,763. For example, thefollowing polymers are biocompatible as well as biodegradable:

DLPLA—poly(dl-lactide)

LPLA—poly(l-lactide)

PGA—polyglycolide

PDO—poly(dioxanone)

PGA-TMC—poly(glycolide-co-trimethylene carbonate)

PGA-LPLA—poly(l-lactide-co-glycolide)

PGA-DLPLA—poly(dl-lactide-co-glycolide)

LPLA-DLPLA—poly(l-lactide-co-dl-lactide)

PDO-PGA-TMC—poly(glycolide-co-trimethylene carbonate-co-dioxanone)

One such class of absorbable material which can be suitable is thepolyhydroxyalkanoate class of biopolymers (“PHA”). For example one suchPHA is produced recombinantly, and branded TephaFLEX polymer, currentlyavailable from Tepha, Inc. Cambridge Mass., USA.

In addition, a biodegradation region can be engineered into a widevariety of biocompatible polymers. Hydrolytically unstable linkages canbe manufactured into biocompatible polymers, such as includingfunctional groups containing esters, anhydrides, orthoesters, andamides. Enzymatic substrate sites, hydrolysis site, or other chemically(or bio-chemically) breaking sites can be incorporated into abiocompatible polymeric backbone otherwise having desiredphysico-chemical properties. Environmental degradation sites, such aslight or temperature sensitive sites, can also be used. For example, onecan employ a chemical moiety which is degraded upon exposure to light,and fiber optic light may be used as the light source for suchdegradation in situ.

The factors affecting the mechanical performance of biodegradablepolymers are those that are well known in the art, and include monomerselection, polymerization initiator selection, process conditions, andthe presence of additives. These factors in turn influence the polymer'shydrophilicity, crystallinity, melt and glass-transition temperatures,molecular weight, molecular-weight distribution, end groups, sequencedistribution (random versus blocky), and presence of residual monomer oradditives. In addition, each of these variables may affect the rate ofbiodegradation.

Alternatively, the tip can be formed of a material which is DMSOdissolvable, allowing it to degrade during a procedure using Onyxthereby lowering the detachable tip tensile strength.

The detachable tips described herein can also optionally be comprised offunctional moieties, such as a detectable label or marking/imagingmoiety. A detectable label or imaging moiety may be incorporated intothe tip composition so that the presence, location, or degree ofdegradation or absorption may be monitored. The label or imaging moietyshould be distinct from any other label or imaging moieties which may bedelivered incident to the use of the catheter, so as to distinguish fromthe catheter delivery and the detachable tip.

The detachable tip can also contain one or more biologically activemoieties, such as a therapeutic moiety. For example, one may wish todeliver an antibiotic or an analgesic at the location where the tip isremoved. Incorporation of a biologically active moiety, including atherapeutically active moiety, into the composition of the detachabletip in essence renders the detachable tip a drug delivery vehicle. Thecomposition of the detachable tip can be selected for a desiredpharmacokinetic or sustained duration drug delivery in addition to anytherapeutic delivery incident to the catheter use.

Biologically active moieties may or may not be therapeuticallyeffective. Although a biological activity can occur locally, this can besolely to inhibit, for example, a later condition from developing or asa prophylactic measure. Thus, any individual patient may or may not showtherapeutic benefit, as the benefit may be the prevention of a harmfulinflammatory response, for example.

Biologically active moieties can be selected from among: analgesicagents, anti-inflammatory agents, antibacterial agents, antiviralagents, antifungal agents, antiparasitic agents, tumoricidal oranti-cancer agents, proteins, toxins, enzymes, hormones,neurotransmitters, glycoproteins, immunoglobulins, immunomodulators,dyes, radiolabels, radiopaque compounds, fluorescent compounds,polysaccharides, cell receptor binding molecules, anti-glaucomic agents,mydriatic compounds, local anesthetics, and angiostatic agents such asendostatin and related agents.

The biologically active ingredient can be a cytokine, a peptidomimetic,a peptide, a protein, a toxoid, a serum, an antibody, a vaccine, anucleoside, a nucleotide, a portion of genetic material, a nucleic acid,or a mixture thereof. In particular, where a catheter tip so removed isleft in place at the site of vasculature repair, a tissue repair moietymay be included, such as a moiety involved in wound healing. Woundhealing acutely involves the release of growth factors and cytokines,but also involves growth factors and tissue repair proteins, epidermalor vascular growth factors (or analogs thereof, such as recombinantlyproduced), hematopoietic factors, such as granulocyte colony stimulatingfactor, stem cell factor, or others and analogs thereof), plateletderived growth factors, fibroblast growth factors, and other naturallyoccurring or synthetic wound healing moieties. In addition, a bloodthinner or anticoagulant, such as coumadin or heparin (or syntheticversions thereof) may be used.

Additional moieties can include microtubule inhibiting moieties (ofwhich anti-tubulin moieties are a species). Microtubules are necessaryfor cytoskeletal and therefore cellular growth or division. Byinhibiting cellular cytoskeletal growth, one may inhibit inflammatory orother unwanted cellular activity. One may inhibit microtubule growth bypreventing inhibiting the tubule formation or by inhibiting the tubuledeconstruction. Various microtubule inhibitors include anti-cancercompounds (taxanes and the vinca alkaloids, for example) as well asother synthetic antitubulin or microtubule inhibitors.

FIG. 15 is a schematic side view illustrating a microcatheter 260 inaccordance with one embodiment. The microcatheter 260 can comprise atubular body 262, a detachable tip 264, and means 266 coupling the tip264 to the tubular body 262. Means 66 can be adapted be able to detachthe tip 264 from the tubular body 262.

The tubular body 262 can include a proximal portion 268 which is closerto an operator of the microcatheter 260, a distal portion 270, and alumen (not shown) extending from the proximal portion 268 to the distalportion 270. The tubular body 262 can have a substantially uniform wallforming the lumen.

Detachment means 266 can be designed to be breakable to detach tip 264from the tubular body 262 for most in vivo applications of themicrocatheter 260. For example, the detachment means 26 can be breakableupon application of a force of about 10 to 160 gram-force.Alternatively, the detachment means can be designed to be breakable byelectrical means. In some embodiments, the detachment means 266 can bean extension of the tubular body 264 and constructed from the samematerial of the tubular body 262. In such cases, the detachment means266 can include a side wall that has a thickness smaller than the wallthickness of the tubular body 64. Alternatively, the detachment means 66can be constructed from a different material from that making thetubular body 62.

In some embodiments, the detachment means 266 can comprise the sleeve 26or 126 described above. In some embodiments, the detachment means 266can be a detachment ring (not shown) that is embedded in the side wallof the tubular body 264. The detachment ring can serve as a point ofweakness which affects detachment of the tip 264. The detachment ringcan also be coupled to a guidewire (not shown) under control of anoperator, which, when effected, causes the detachment of the tip 264from the tubular body 262. Alternatively, the detachment ring can bemade of an electrically resistive material which when an electricalcurrent passes therethrough, heats the tip 264 causing the detachment oftip 64 from the tubular body 62.

Other embodiments of detachment means 266 are also possible. Forexample, the detachment means 266 can be a receiving structure such as aflange formed at the distal end of the tubular body 262 into which thetip 264 is fitted, or the detachment means 266 can be a heat or pressurebonding providing a predetermined bond strength between the tip 264 andthe tubular body 262. The bonding can be broken upon application of apredetermined force.

The tip 264 can be provided with a channel (not shown) which is in fluidcommunication with the lumen of the tubular body and has at least oneopening for delivering an embolic agent to a site in the vasculature.The tip 264 can have a plurality of openings 272 on the side wall of thetip for delivering the fluid agent. The tip 264 can also have an openingat the distal end of the tip for delivering the embolic agent. The tip264 can be constructed from a material that is biodegradable.Alternatively, the tip 264 may be made of a material which is notbiodegradable. Various materials, designs, compositions, and functionshave been described above in connection with detachable tips, which areequally applicable to the tip 264 in this embodiment.

A marker or marker band 274 can be provided on the distal portion 270 ofthe tubular body 262. The marker band 274 can be disposed immediatelyproximal to the detachment means 266 to assist an operator to visualizethe location of the detachable tip 264 and/or the detachment zone 266inside the vascular system. The marker band 274 can be made of aradiopaque metal which can be identified by for example X-ray imaging.Since the marker band 274 is disposed on the tubular body 262, itremains on the tubular body 272 after the tip 264 is detached from thetubular body 62. As a result, the marker band 274 or the radiopaquemetal can be removed out of the patient with the tubular body 62 afterdelivery of the fluid agent, thus minimizing or eliminating damages tothe patient.

A second marker or marker band 276 can be provided on the tip 264. Theadditional marker band 276 can be disposed immediately proximal to thedistal end of the tip 264 and thus remains at the site of delivery afterthe tip 264 is detached from the tubular body 262. In cases that themicrocatheter 260 is used for delivering an embolic agent for treatingan aneurysm, a solid mass can be formed from the embolic agent in situ.As a result, the additional marker band 276 can be embedded in the solidmass at the embolization site and does not enter the systemic fluid ofthe treated vascular, which is otherwise detrimental to the patient.

The attachment means can comprise a flange structure adapted to couplethe tip body to the tubular body. The tip body can be made of a materialthat is biodegradable.

ADDITIONAL EXAMPLES

Presented below are additional examples illustrating methods of use fordelivery of an embolic composition. These examples are merely forillustrative purposes, and are not intended to be limiting.

Example 1 Use of Detachable Biodegradable Tip

This example illustrates how one can embolize a blood vessel using acatheter. The term “embolizing” refers to a process wherein a materialis injected into a blood vessel, typically to plug the vessel to stopunwanted blood flow. Materials and methods for embolizing are set forthin U.S. Pat. No. 5,695,480, herein incorporated by reference in itsentirety and made a part of this specification. Alternatively, materialsfor embolization can be purchased from ev3 Neurovascular Inc., Irvine,Calif., USA. Examples include Onyx® embolic compositions sold as Onyx®18, 20, 34 and 500 HD embolic compositions. For example, where a humanpatient has an aneurysm in the brain, embolizing materials set forth inU.S. Pat. No. 6,454,738 can be delivered to the site of the aneurysm viaa catheter.

As noted above, one commercially available embolic agent is Onyx® andits associated kit, the Onyx® Liquid Embolic System sold by ev3Neurovascular, Inc. (MicroTherapeutics, Inc., Irvine, Calif., USA).

The embolic Onyx® compositions in the kits can be non-adhesive liquidembolic agents comprised of EVOH (ethylene vinyl alcohol) copolymerdissolved in DMSO (dimethyl sulfoxide) and suspended micronized tantalumpowder to provide contrast for visualization under fluoroscopy. TheOnyx® embolic agents can be both biologically active agents as well ascontain a diagnostic or imaging agent.

In some embodiments, such as with microcatheter 110, it is preferred touse an Onyx® 18 or 34 kit. Onyx® 18 and 34 kits can include a 1.5 mlvial of Onyx® embolic agent, a 1.5 ml vial of DMSO, one DMSO-compatibledelivery syringe, and two Onyx® syringes. Onyx® 18 or 34 can bedelivered by slow controlled injection through a microcatheter into theaneurysm or other vascular site under fluoroscopic control. The DMSOsolvent can dissipate into the blood, causing the EVOH copolymer andsuspended tantalum to precipitate in situ into a spongy, coherentembolus. The Onyx® 18 or 34 can immediately form a skin as the polymericembolus solidifies from the outside to the inside, while filling moredistally in the vascular site. Final solidification of this material canoccur within five minutes.

A microcatheter having a predetermined tip detachment area as disclosedherein can be used to deliver the Onyx® embolic agent. Immediatelyproximal to the detachment area, or within the detachment area, can be amarker band. This band, which can be around or in the tubular body, canbe continuous or discontinuous. In some embodiments, the microcathetertubular body can be of uniform elasticity and plasticity except for aregion approximately 1 cm from the distal end (e.g. the tip body of aunibody-constructed catheter). In some embodiments, the tip bodies 30described herein can be between 1-10 cm in length, preferably between1-6 cm in length, and even more preferably between 1-3 cm in length.Other ranges are also possible. The diameter of the microcathetertubular body at 1 cm from the distal end can, for example, be betweenabout 0.5 mm and about 1.5 mm. Other diameters and ranges are alsopossible. Additionally, at a distance, for example, of about 1-10 cmfrom a distal end of the distal tip the microcatheter body can contain apredetermined detachment area of lower plasticity and elasticity.Optionally this region can be biodegradable.

The practitioner will recognize that the distances, diameters, and otherdimensions described above may vary depending on the type of catheterand the use to which the catheter will be put.

Example 2 Use of Detachable Biodegradable Tip

The catheter in Example 1 can be used, wherein the predetermined tipdetachment area is a separate tip fitted over the distal end of thecatheter as a sleeve, as illustrated in FIG. 12. The separate tip can becomprised of a biocompatible, biodegradable polymer. The biodegradablepolymer can contain enzymatic degradation sites which, in the presenceof a suitable enzyme, degrade the tip to bioabsorbable constituents.

Example 3 Use of Detachable Tip Having Grips for Mechanical Retrieval

A tip as shown in FIG. 14, with grippable elements, can be removed fromthe catheter. A guidewire or other mechanical element can be used tostabilize or retrieve the tip having grippable elements. The tip canthen be inhibited from migrating in the systemic circulation orembedding in the vasculature. The tip so stabilized can be kept at itsin situ location for local deployment of any other moiety, such as animaging agent or biologically active moiety, if the tip has suitabledelivery properties as described herein or known in the art. Forexample, active agents (such as biologically active agents) can beaffixed to the tip non-covalently, for release in an aqueous environmentunder suitable conditions as is available.

Example 4 Use of Detachable Tip Containing Imaging Agents

A distal tip (or separate detachable tip) can further comprise anadditional detectable label or imaging reagent. The practitioner canobserve the degradation or subsequent absorption by suitable labeldetection (e.g., florescent labels detected via light sensor) or imagingviewing (e.g., a contrast agent which can be distinguished from theembolic agent).

Example 5 Use of Detachable Tip Containing Additional BiologicallyActive Moiety

A catheter can have a predetermined tip detachment area at, for example,10 mm from the distal end. The tip portion of the catheter body (or, aseparate tip) can be biodegradable and can act as a sustained releasedelivery vehicle for biologically active moieties.

The catheter can be used to selectively deliver an anti-cancerchemotherapeutic agent to a specific location within a patient's bodywhere a tumor is located. After delivery of the primary anti-cancerchemotherapeutic agent, the tip can be deployed at a location proximateto the tumor. The tip can contain a dosage of a second anti-tumorbiologically active agent to be released over a selected duration.

The catheter and compositions described above can also be used in otherembolic situations such as in the embolization of AVM's, in theembolization of blood vessels feeding into malignant and non-malignanttumors such as fibroid tumors, treating blood vessels involved inabdominal aortic aneurysms (AAA), and the like.

Although these inventions have been disclosed in the context of certainpreferred embodiments and examples, it will be understood by thoseskilled in the art that the present inventions extend beyond thespecifically disclosed embodiments to other alternative embodimentsand/or uses of the inventions and obvious modifications and equivalentsthereof. In addition, while several variations of the inventions havebeen shown and described in detail, other modifications, which arewithin the scope of these inventions, will be readily apparent to thoseof skill in the art based upon this disclosure. It is also contemplatedthat various combinations or sub-combinations of the specific featuresand aspects of the embodiments can be made and still fall within thescope of the inventions. It should be understood that various featuresand aspects of the disclosed embodiments can be combined with orsubstituted for one another in order to form varying modes of thedisclosed inventions. Thus, it is intended that the scope of at leastsome of the present inventions herein disclosed should not be limited bythe particular disclosed embodiments described above.

What is claimed is:
 1. A microcatheter for delivering embolic agent to avascular site within a patient comprising: an elongate flexible tubularbody having a proximal end and a distal end and defining at least onetubular body lumen; and a tip body having a proximal end and a distalend and defining a tip body lumen; wherein the tip body is frictionallysupported on the tubular body such that the tip body lumen is in fluidcommunication with the tubular body lumen, the tip body being detachablefrom the tubular body by application of a retraction force.
 2. Themicrocatheter of claim 1, further including a sleeve covering a distalportion of the tubular body and a proximal portion of the tip body,wherein the tip body is frictionally supported on the sleeve and thesleeve is frictionally supported on the tubular body.
 3. Themicrocatheter of claim 2, wherein the sleeve forms a tighter frictionalengagement with the tubular body than with the tip body.
 4. Themicrocatheter of claim 2, further comprising a first marker disposed onthe distal end of the tubular body under the sleeve for indicating aposition of the tip body prior to detachment of the tip body.
 5. Themicrocatheter of claim 4, wherein the first marker is a radiopaquemarker band on an outer surface of the tubular body.
 6. Themicrocatheter of claim 5, further comprising a second marker disposed onthe tubular body for indicating a position of the tip body afterdetachment of the tip body.
 7. The microcatheter of claim 1, wherein thetip body comprises a plurality of holes on a side wall of the tip bodyfor delivering the embolic agent to the vascular site.
 8. Themicrocatheter of claim 2, wherein the sleeve is a thermoplastic selectedfrom the group consisting of thermoplastic polyolefin elastomer(TPE).acrylic; celluloid; cellulose acetate; ethylene-vinyl acetate(EVA); ethylene vinyl alcohol (EVAL); fluoroplastics (PTFE, FEP, PFA,CTFE, ECTFE, ETFE); ionomers; acrylic/PVC alloy; liquid crystal polymer(LCP); polyacetal (POM or Acetal); polyacrylonitrile (PAN oracrylonitrile); polyamide (PA or Nylon); polyarylethkerketone (PAEK orKetone); polybutadiene (PBD); polybutylene (PB); polycaprolactone (PCL);polychlorotrifluoroethylene (PCTFE); polyhydroxyalkanoates (PHAs);polyketone (PK); polyester; low density polyethylene (LDPE); linear lowdensity polyethylene (LLDPE); polyethylene (PE); polyetherimide (PEI);polyethersulfone (PES); polysulfone; polyethylenechlorinates (PEC);polylactic acid (PLA); polymethylpentent (PMP); polyphenylene oxide(PPO); polyphenylene sulfide (PPS); polyphthalamide (PPA0; polypropylene(PP); polystyrene (PS); polyvinyl chloride (PVC); polyvinylidenechloride (PVDC); and combinations thereof.
 9. The microcatheter of claim8, wherein the thermoplastic is a polyolefin.
 10. The microcatheter ofclaim 9, wherein the polyolefin is polyethylene or polyolefin elastomeror combinations thereof.
 11. The microcatheter of claim 1, wherein theretraction force is between approximately 10 to 160 grain-force.
 12. Themicrocatheter of claim 11, wherein the microcatheter has a static burststrength of between about 150 and 400 psi, and the retraction force isbetween about 25 and 40 gram-force.
 13. The microcatheter of claim 1,wherein the sleeve comprises an internal separation element.
 14. Themicrocatheter of claim 1, wherein the tip body is biodegradable.